Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

Is what's causing PEM activity of the brain in excess of what it can tolerate due to some problem at the synapses?

Is there any indication that glutaminergic synapses are playing a role in ME/CFS?

What's the similarity between autism and ME/CFS?
 
Like @forestglip and @ME/CFS Science Blog I’ve spent some time digging into some tools including magma/fuma and annovar. And learnt a bit about the myriad hurdles and technical issues bioinformatics students and researchers must live with. After a week much of my understanding is likely way off but I have a few questions, maybe they’re best for @Chris Ponting and the authors but perhaps others with more experience can chime in?

Were the GWAS summary statistics (hg38) or other/raw data used for MAGMA/FUMA analysis? What reference panel was used? These tools and the default panels seem to depend upon different human genome versions/reference assemblies than hg38, was liftover used or re-calling? I’m unsure about some other settings like the window size too, which could effect things quite a lot.

Knowing more about the methods, data and settings here would help reproducibility and understanding I think. And I wonder about what risks/loss there are with conversions between formats?

This study used an additive model I think, would it be worth exploring results from recessive/dominant models too?

I have learned new words like exonic, intronic and intergenic and as far as I can tell most findings (88%) from GWAS studies are in these interonic and intergenic regions. Although these don’t directly change the protein, it seems they can modify things a lot by effecting expression through things like translation.

There seems lots of scope for more analysis here, understanding what is in LD with the identified SNPs and using more tools like annotation to help get an idea of potential mechanisms. Or did the eQTL and risk loci cover this? I’ve not started looking at that yet and don’t understand the pros/cons of different methods.

Is this sort of wider analysis planned? Is the hope others may take it up? Would it be possible to make more of the data available to help others do this?

A bit of a mishmash of questions and thoughts….
 
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